Aluminum toxicity has been implicated in the aetiology of a variety of disorders, in particular in the bone and the brain, following occupational and theraupeutic exposure of patients. Furthermore, in the environment aluminum may enter the food chain via plants and fish taking up aluminum mobilized from acid- sensitive soils by atmospheric deposition. Since scant information is available on molecular processes related to aluminum toxicity, the overall objectives of this proposal are to provide an integrated picture of aluminum interactions with the plasma membrane, intracellular aluminum accumulation and cell viability. Mouse neuroblastoma cells are selected because aluminum concentratins can be applied to cultured cell sin a defined manner. The specific, interrelated goals of this proposal are: (I) Determine physico-chemical changes (phase changes, microviscosity) in the plasma membrane of neuroblastoma cells in response to micromolar aluminum stress. Assess the role of calcium ions in modulating the impact of deleterious aluminum ions on membrane properties. Examine the influence of highly stable aluminum complexes, specifically aluminum citrate, on structural changes in the plasma membrane. The experiments planned are executed by applying spin and fluorescence probes which serve to monitor the membrane's physical state via metal-induced changes in the probe's motional properties. (II) Determine the amount and kinetics of intracellular aluminum accumulation, measured with an atomic absorption spectrophotometer, in response to aluminum stress. Correlate aluminum accumulation with cell viability, evaluate by applying vital stains, and the physical state of the cell's plasma membrane. The long-range goal is to develop a molecular understanding of aluminum toxicity, especially the role of the plasma membrane and crucial regulatory proteins like calmodulin. Experiments with aluminum chelates will hopefully generate knowledger helpful indeveloping a strategy for an efficient therapy of aluminum toxicity syndromes.